Determination of protein secondary and tertiary structure is currently limited to two techniques: x-ray crystallography and nuclear magnetic resonance spectroscopy. A new chemical method is proposed for identification of flexible loops or random coil regions of proteins in contrast to highly structured alphahelices and beta-sheets. Such a method would readily provide structural information in proteins for which crystallographic or NMR analysis is not practical. Furthermore, it may serve as a dynamic conformational probe to learn about the flexibilty of certain regions of a protein. The technique relies upon the intrinsic ability of certain metal ions, Ni 2+, CU2+ and Pd 2+, to bind to the peptide backbone via deprotonation of amide nitrogens. Under non-denaturing conditions, only the most flexible regions are proposed to be susceptible to metal ion coordination. Once coordinated to a peptidic ligand, Ni-II (for example) may react with an oxidant resulting in hydroxylation of a C-alpha at the ligation site and rendering the protein sensitive to mild hydrolytic conditions. It is therefore proposed that the protein will be cut into domains such that scission occurs at flexible loops or random coil regions. Identification of loops vs. highly organized domains will aid in the understanding of structure/function relationships in proteins. Experiments proposed here will focus upon oxidative cleavage of proteins in the presence of metal ions. Proteins will be studied whose crystallographic structures have been determined in order to test the hypothesis. Protein fragments will be analyzed by gel electrophoresis and standard sequencing techniques.